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NOX4-Dependent Hydrogen Peroxide Overproduction in Human Atrial Fibrillation and HL-1 Atrial Cells: Relationship to Hypertension.

Zhang J, Youn JY, Kim AY, Ramirez RJ, Gao L, Ngo D, Chen P, Scovotti J, Mahajan A, Cai H - Front Physiol (2012)

Bottom Line: Patients with AF were older than those without (58.8 ± 11.7 vs. 47.8 ± 19.2, p = 0.047).Whereas total [Formula: see text] production (determined by electron spin resonance) was similar in patients with and without AF, H(2)O(2) production was more than doubled in AF patients (149.8 ± 26.28 vs. 66.9 ± 7.14 pmol/mg/min, p = 0.0055), which correlated well with a doubling in NOX isoform 4 (NOX4) expression.AF patients with co-existing hypertension had three-fold higher H(2)O(2) production compared to those without (239.0 ± 125.1 vs. 83.6 ± 51.3 pmol/mg/min, p = 0.003).

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Medicine, Cardiovascular Research Laboratories, Department of Anesthesiology, David Geffen School of Medicine at University of California Los Angeles Los Angeles, CA, USA.

ABSTRACT

Background/objectives: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia with patients dying frequently of stroke. In view of the unclear etiologies of AF and a potential role of oxidative stress, the present study examined cardiac reactive oxygen species production and NADPH oxidase (NOX) expression in AF patients.

Methods and results: Patients with AF were older than those without (58.8 ± 11.7 vs. 47.8 ± 19.2, p = 0.047). Whereas total [Formula: see text] production (determined by electron spin resonance) was similar in patients with and without AF, H(2)O(2) production was more than doubled in AF patients (149.8 ± 26.28 vs. 66.9 ± 7.14 pmol/mg/min, p = 0.0055), which correlated well with a doubling in NOX isoform 4 (NOX4) expression. AF patients with co-existing hypertension had three-fold higher H(2)O(2) production compared to those without (239.0 ± 125.1 vs. 83.6 ± 51.3 pmol/mg/min, p = 0.003). Treatment of HL-1 atrial cells with angiotensin II, a known modulator of atrial structural remodeling, resulted in upregulation of NOX4 and H(2)O(2) production, further implicating a potential role of NOX4 in atrial remodeling.

Conclusion: Our data represent the first implication that NOX4-derived H(2)O(2) may play an important role in the etiologies of AF.

No MeSH data available.


Related in: MedlinePlus

Upregulation of NOX4 expression and its correlation with hydrogen peroxide production in patients with atrial fibrillation. (A) NOX4 mRNA expression. NOX4 mRNA expression was determined by RT-PCR analysis and normalization to endogenous amplicon of GAPDH. (B) Correlation between NOX4 mRNA expression and hydrogen peroxide production.
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Figure 2: Upregulation of NOX4 expression and its correlation with hydrogen peroxide production in patients with atrial fibrillation. (A) NOX4 mRNA expression. NOX4 mRNA expression was determined by RT-PCR analysis and normalization to endogenous amplicon of GAPDH. (B) Correlation between NOX4 mRNA expression and hydrogen peroxide production.

Mentions: NOX4 is known to either produce H2O2 directly, or produce in subcellular organelles leaving membrane permeable H2O2 the sole detectable species (Martyn et al., 2006; Lambeth et al., 2007; Serrander et al., 2007; Chen et al., 2008; Block et al., 2009; Lassegue and Griendling, 2010). Other NOX isoforms however, have been shown to produce directly (Choi et al., 2008). Intriguingly, NOX4 mRNA expression was found significantly upregulated in AF patients (Figure 2A), which correlated well with a marked increase in H2O2 production (Figure 2B). The expression of NOX1 and NOX2 however, was not different in patients with and without AF (Figures 3A,B). NOX3 and NOX5 were not detectable in LAA. We did not find any correlation between ejection fractions and NOX4/H2O2 levels in both groups. This indicates that severity of heart failure is not linked to NOX4-H2O2 axis as AF does.


NOX4-Dependent Hydrogen Peroxide Overproduction in Human Atrial Fibrillation and HL-1 Atrial Cells: Relationship to Hypertension.

Zhang J, Youn JY, Kim AY, Ramirez RJ, Gao L, Ngo D, Chen P, Scovotti J, Mahajan A, Cai H - Front Physiol (2012)

Upregulation of NOX4 expression and its correlation with hydrogen peroxide production in patients with atrial fibrillation. (A) NOX4 mRNA expression. NOX4 mRNA expression was determined by RT-PCR analysis and normalization to endogenous amplicon of GAPDH. (B) Correlation between NOX4 mRNA expression and hydrogen peroxide production.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3367314&req=5

Figure 2: Upregulation of NOX4 expression and its correlation with hydrogen peroxide production in patients with atrial fibrillation. (A) NOX4 mRNA expression. NOX4 mRNA expression was determined by RT-PCR analysis and normalization to endogenous amplicon of GAPDH. (B) Correlation between NOX4 mRNA expression and hydrogen peroxide production.
Mentions: NOX4 is known to either produce H2O2 directly, or produce in subcellular organelles leaving membrane permeable H2O2 the sole detectable species (Martyn et al., 2006; Lambeth et al., 2007; Serrander et al., 2007; Chen et al., 2008; Block et al., 2009; Lassegue and Griendling, 2010). Other NOX isoforms however, have been shown to produce directly (Choi et al., 2008). Intriguingly, NOX4 mRNA expression was found significantly upregulated in AF patients (Figure 2A), which correlated well with a marked increase in H2O2 production (Figure 2B). The expression of NOX1 and NOX2 however, was not different in patients with and without AF (Figures 3A,B). NOX3 and NOX5 were not detectable in LAA. We did not find any correlation between ejection fractions and NOX4/H2O2 levels in both groups. This indicates that severity of heart failure is not linked to NOX4-H2O2 axis as AF does.

Bottom Line: Patients with AF were older than those without (58.8 ± 11.7 vs. 47.8 ± 19.2, p = 0.047).Whereas total [Formula: see text] production (determined by electron spin resonance) was similar in patients with and without AF, H(2)O(2) production was more than doubled in AF patients (149.8 ± 26.28 vs. 66.9 ± 7.14 pmol/mg/min, p = 0.0055), which correlated well with a doubling in NOX isoform 4 (NOX4) expression.AF patients with co-existing hypertension had three-fold higher H(2)O(2) production compared to those without (239.0 ± 125.1 vs. 83.6 ± 51.3 pmol/mg/min, p = 0.003).

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Medicine, Cardiovascular Research Laboratories, Department of Anesthesiology, David Geffen School of Medicine at University of California Los Angeles Los Angeles, CA, USA.

ABSTRACT

Background/objectives: Atrial fibrillation (AF) is the most common type of cardiac arrhythmia with patients dying frequently of stroke. In view of the unclear etiologies of AF and a potential role of oxidative stress, the present study examined cardiac reactive oxygen species production and NADPH oxidase (NOX) expression in AF patients.

Methods and results: Patients with AF were older than those without (58.8 ± 11.7 vs. 47.8 ± 19.2, p = 0.047). Whereas total [Formula: see text] production (determined by electron spin resonance) was similar in patients with and without AF, H(2)O(2) production was more than doubled in AF patients (149.8 ± 26.28 vs. 66.9 ± 7.14 pmol/mg/min, p = 0.0055), which correlated well with a doubling in NOX isoform 4 (NOX4) expression. AF patients with co-existing hypertension had three-fold higher H(2)O(2) production compared to those without (239.0 ± 125.1 vs. 83.6 ± 51.3 pmol/mg/min, p = 0.003). Treatment of HL-1 atrial cells with angiotensin II, a known modulator of atrial structural remodeling, resulted in upregulation of NOX4 and H(2)O(2) production, further implicating a potential role of NOX4 in atrial remodeling.

Conclusion: Our data represent the first implication that NOX4-derived H(2)O(2) may play an important role in the etiologies of AF.

No MeSH data available.


Related in: MedlinePlus